In recent years, there is the highest mortality rate from malignant tumors mainly comprising cancers in various countries and, therefore, it has been urgently required to establish effective therapeutics therefor. The known methods for treating malignant tumors include surgical extraction, radiotherapeutics, and subsequent maintenance therapeutics with the use of antibiotics, vegetable alkaloids or synthetic anticancer drugs. However, no satisfactory treatment has been established for, in particular, solid cancer.
The present inventors previously found that an antifungal microbial metabolite SF2698 as described in EP-A-458259 has an antitumor activity (Proceedings of 50th General Meeting of Japan Society of Cancer, page 2065, 1991).
With the progress in studies on cancer genes, a number of oncogenes have been found in human cancers. Among these oncogenes, ras gene is activated through one point mutation in various human cancers in, for example, pancreas, intestinum crassum, lung, stomach and skin, though healthy subjects carry this ras gene in a normal state. Accordingly, it is considered that the ras gene might relate to canceration in human and the malignancy of cancers. In order to find a novel carcinostatic substance, the present inventors screened various compounds by assaying the inhibitory effect on the growth of mouse NIH3T3 cells which had been transformed with activated c-Ha-ras gene isolated from a tumor of a human patient with melanoma. As a result, it was found that L-.beta.-(5-hydroxy-2-pyridyl)alanine (azatyrosine) selectively inhibited the growth of NIH3T3 cells transformed with the activated ras gene at a concentration of 500 .mu.g/ml but never inhibited the growth of normal NIH3T3 cells at the same concentration. It was further found that cells surviving after treatment with azatyrosine were revertant cells (JP-A-1-110627, the term "JP-A" as used herein means an "unexamined Japanese patent application").